Abstract
We present results of 2 similarly designed but separate phase 2 studies involving single-agent lenalidomide (CC-5013, Revlimid) in a total of 68 patients with symptomatic myelofibrosis with myeloid metaplasia (MMM). Protocol treatment consisted of oral lenalidomide at 10 mg/d (5 mg/d if baseline platelet count < 100 x 10(9)/L) for 3 to 4 months with a plan to continue treatment for either 3 or 24 additional months, in case of response. Overall response rates were 22% for anemia, 33% for splenomegaly, and 50% for thrombocytopenia. Response in anemia was deemed impressive in 8 patients whose hemoglobin level normalized from a baseline of either transfusion dependency or hemoglobin level lower than 100 g/L. Additional treatment effects in these patients included resolution of leukoerythroblastosis (4 patients), a decrease in medullary fibrosis and angiogenesis (2 patients), and del(5)(q13q33) cytogenetic remission accompanied by a reduction in JAK2(V617F) mutation burden (1 patient). Grade 3 or 4 adverse events included neutropenia (31%) and thrombocytopenia (19%). We conclude that lenalidomide engenders an intriguing treatment activity in a subset of patients with MMM that includes an unprecedented effect on peripheral blood and bone marrow abnormalities.
Publication types
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Clinical Trial, Phase II
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Multicenter Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Administration, Oral
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Adult
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Aged
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Anemia / blood
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Anemia / complications
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Anemia / drug therapy
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Anemia / genetics
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Anemia / pathology
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Anemia, Myelophthisic / blood
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Anemia, Myelophthisic / complications
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Anemia, Myelophthisic / drug therapy
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Anemia, Myelophthisic / genetics
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Anemia, Myelophthisic / pathology
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Female
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Hemoglobins / analysis
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Humans
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Janus Kinase 2
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Lenalidomide
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Male
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Neovascularization, Pathologic / blood
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Neovascularization, Pathologic / complications
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Neovascularization, Pathologic / drug therapy
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Neovascularization, Pathologic / genetics
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Neovascularization, Pathologic / pathology
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Neutropenia / blood
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Neutropenia / chemically induced
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Neutropenia / genetics
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Neutropenia / pathology
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Platelet Count
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Point Mutation
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Primary Myelofibrosis / blood
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Primary Myelofibrosis / complications
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Primary Myelofibrosis / drug therapy*
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Primary Myelofibrosis / genetics
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Primary Myelofibrosis / pathology
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Protein-Tyrosine Kinases / genetics
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Proto-Oncogene Proteins / genetics
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Remission Induction
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Sequence Deletion
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Splenomegaly / blood
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Splenomegaly / complications
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Splenomegaly / drug therapy
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Splenomegaly / genetics
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Splenomegaly / pathology
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Thalidomide / administration & dosage
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Thalidomide / adverse effects
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Thalidomide / analogs & derivatives*
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Thrombocytopenia / blood
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Thrombocytopenia / chemically induced
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Thrombocytopenia / drug therapy
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Thrombocytopenia / genetics
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Thrombocytopenia / pathology
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Time Factors
Substances
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Hemoglobins
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Proto-Oncogene Proteins
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Thalidomide
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Protein-Tyrosine Kinases
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JAK2 protein, human
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Janus Kinase 2
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Lenalidomide